Acupuncture has been increasingly used as a modality of complementary and alternative medicine for treating clinical conditions including pain. However, the clinical effectiveness of acupuncture therapy remains difficult to assess. In search for informative and clinically relevant outcome measures for acupuncture therapy, it is important to make a distinction between clinical outcome measures and those measures reflective of the acupuncture's effect on biological (e.g., biomarkers) and/or physiological responses. A translational tool useful to assess the effectiveness of acupuncture therapy should be expected to bridge the gap between preclinical and clinical studies of acupuncture as well as between conventional medicine and alternative medicine. In this regard, quantitative sensory testing (QST) is a well-recognized psychophysical outcome measure that has been extensively used to assess the effect of conventional medicine on clinical pain. QST provides valuable information on both pain intensity and pain affect and, when combined with other clinical tools (e.g., pain inventory), can be used as a standard research and clinical tool. To date, QST has rarely been used as an outcome measure for clinical acupuncture therapy. In this application, we propose to develop a new approach to evaluating the effectiveness of acupuncture therapy by integrating the unique psychophysical features of QST responses (QST responders) with clinical evidence for pain symptom relief (clinical responders). This approach will be used to differentiate between the acupuncture's physiological and biological effect and its effect on clinical pain symptom relief. This proposed approach will be examined through a set of integrated and complementary experiments as outlined in four specific aims: (1) To evaluate QST as an assessment tool for the effect of acupuncture versus sham acupuncture on clinical pain; (2) To explore the role of QST in acupuncture outcome measures between acupuncture believers and acupuncture non-believers; (3) To compare the effect of acupuncture versus conventional medicine on clinical pain using a standard QST protocol; and (4) To compare changes in QST responses and biomarkers for nociception (e.g., interleukins) and antinociception (e.g., -endorphin) in pain subjects before and after acupuncture therapy. This research project will yield valuable information on a research and clinical assessment tool that could be used to compare the therapeutic effect on clinical pain between acupuncture (other forms of alternative medicine as well) and conventional medicine. PUBLIC HEALTH RELEVANCE: In recent years, acupuncture has gained its popularity in the United States of America as a modality of complementary and alternative medicine for treating many clinical conditions including pain. However, the clinical effectiveness of acupuncture therapy remains difficult to assess. In this project, a new approach will be developed to evaluate the effectiveness of acupuncture therapy. This new approach could be used to compare the therapeutic effects on clinical pain between acupuncture (other forms of alternative medicine as well) and conventional medicine.